Fall 1996 Volume 1, Number 4		ACIP wrestles with combination vaccines (Atlanta) As new combination vaccines continue to appear on pharmacy shelves, the Advisory Committee on Immunization Practices (ACIP) is wrestling with the implications of these products for the nation's childhood immunization schedule. Two new vaccine combinations were licensed in 1996, DTaP-Hib and Hib-HepB (see Comvax™ story in this issue). Over 20 other new combination products are expected in the next few years, including several that contain hepatitis antigens: DTaP-HepB, DTaP-Hib-HepB, DTaP-HepB-IPV, Hib-HepB-IPV, DTaP-Hib-HepB-IPV, DTaP-Hib-HepB-IPV-HepA, and HepB-HepA. Discussions at February ACIP meeting At its February meeting in Atlanta, ACIP heard a presentation on the issue from a special subcommittee, the ACIP Combination Vaccine Working Group, and heard comments from ACIP liaison and audience members. The Working Group observed that, as the number of new combination products mushrooms, no immunization provider will be able to stock more than a few combination products. Instead, providers will have to choose a "package" of combination vaccines that best meets the needs of their patients. In choosing such a package, providers must consider the need to maximize safety and effectiveness, the need to minimize costs, and the need to keep the product stock as simple as possible. Providers must also balance the ability to interchange antigens as much as possible against the need to use a single brand for some immunization series, such as acellular pertussis vaccine. Combination vaccines have the potential to lower immunization costs, to reduce the number of needlesticks needed (which may enable the addition of new antigens), and to increase coverage rates. But they also have the potential to create what one ACIP member called "combination chaos" by actually increasing the number of products that must be stocked and thereby raising costs, by reducing interchangeability between brands, by complicating record keeping and reimbursement, and by making the immunization schedule so complex that providers are unable to comprehend it. According to the Working Group, the combination vaccine issue is complicated further by the fact that many children switch providers during the first two years of life. In the coming era of multiple combination vaccines, when a child switches providers, the new provider will probably have to continue the child's immunization schedule using a different choice of products than used by the old provider, while also trying to make sense of the previous combinations received. This is no small problem - one-quarter of all U.S. children change providers before the age of two. It may be especially severe for Medicaid-insured children in managed care, who change providers on the average of every 9-10 months. Another problem is presented by children who start vaccinations late. Accelerated schedules vary by individual antigen and may not be accommodated by the combinations that a provider has available. Launch of Hib-HepB combination raises questions about extra HB vaccine dose The recent introduction of a three-dose Hib-HepB combination vaccine has presented ACIP with many of the issues it will confront in the future as more combinations reach the market (see story in this issue of HCR). Comvax™ allows providers to reduce the number of needlesticks received by a child by as much as four (from 15 to 11), thereby reducing the pain and cost of injections and increasing compliance. It can also decrease the number of products that an immunization clinic needs to stock. But because Comvax™ cannot be used in children less than six weeks old for reasons related to its Hib component, it cannot be used for the birth dose of hepatitis B vaccine. Thus, for children who begin the hepatitis B vaccination series at birth or soon thereafter, the use of Comvax™ alone would necessitate an extra, fourth dose of hepatitis B antigen at age 12-15 months (That is, the birth dose of hepatitis B vaccine plus three doses of Comvax™). Only three doses of the currently-available monovalent hepatitis B vaccines are required. A fourth dose of hepatitis B antigen is not medically harmful - it carries no increased risk of adverse events. Its main disadvantage seems to be extra cost, including the cost of Comvax™ and the cost of an extra dose of antigen. However, at the February ACIP meeting, CDC staff minimized this, saying that costs associated with the administration of an extra dose of hepatitis B vaccine "do not appreciably alter the favorable cost effectiveness of routine infant immunization with hepatitis B vaccine." To avoid the fourth dose of hepatitis B antigen, a provider could give Comvax™ at 2 and 12-15 months of age, and give monovalent Hib vaccine at the 4 month visit. But this adds complexity to the vaccination schedule and necessitates the stocking of monovalent Hib vaccine, annulling some of the advantages of the combination vaccine. Alternatively, a provider could drop the birth dose of hepatitis B vaccine (while still conducting the recommended screening for HBsAg-seropositive mothers) and give the entire hepatitis B series using Comvax™ beginning at 2 months of age. However, CDC staff and ACIP members did not favor dropping the birth dose of hepatitis B because they consider the dose a hard-won and important public health intervention. Currently, 40% of U.S. children receive a birth dose. It decreases the number of injections a child must receive during follow-up visits and probably prevents perinatal hepatitis B in some infants whose mothers were not screened for HBsAg (hepatitis B vaccine alone, without hepatitis B immune globulin, is highly effective in preventing infection in infants born to carrier mothers). Combination vaccine issue is here to stay ACIP plans to continue studying the implications of new combination vaccines and may issue a recommendation on the subject later this year. The Committee will probably come out generally in favor of combination vaccines. It may specify that the administration of unneeded antigen doses is acceptable when the use of a combination is safe and is justified on public health grounds (to lower cost, maintain coverage, etc.). The Committee may also urge that insurers cover all vaccine products, including monovalent ones, in order to give providers maximum flexibility. It may also urge insurers to guarantee reimbursement for "good faith" duplicate vaccinations or extra antigen doses. Further, the Committee is considering the development of a new standardized immunization form or other innovations to make maintenance of the vaccine schedule easier when a child changes providers. As said by ACIP Chairman Dr. Jeffrey P. Davis, "we are all struggling with the rapidity with which vaccines can be manufactured in combination."